Proteomics-based interrogation of the kinome and its implications for precision oncology
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Updated: Nov 18, 2025
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Published on: September 19, 2018
Terry C C Lim Kam Sian1, Anderly C Chüeh1, Roger J Daly1
1Cancer Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Abstract:
The identification of specific protein kinases as oncogenic drivers in a variety of cancer types, coupled with the clinical success of particular kinase-directed targeted therapies, has cemented the human kinome as an attractive source of "actionable" targets for cancer therapy. However, "mining" of the human kinome for precision oncology applications has yet to yield its full potential. This reflects a variety of issues, including oncogenic kinase dysregulation at levels not detectable by genomic sequencing and the uncharacterized nature of a considerable fraction of the kinome. In addition, selective therapeutic targeting of specific kinases requires efficient mapping of total kinome space impacted by candidate small molecule drugs. Fortunately, recent developments in proteomics techniques, particularly in mass spectrometry-based phosphoproteomics and kinomics, provide the necessary technology platforms to address these impediments. Moreover, initiatives such as the Clinical Proteomic Tumour Analysis Consortium have enabled the generation, deposition and integration of genomic, transcriptomic and (phospho)proteomic data for many cancer types, providing unprecedented insights into oncogenic kinases and cancer cell signalling generally. These multi-omic data are identifying novel therapeutic targets, highlighting opportunities for drug re-purposing, and helping assign optimal therapies to specific tumour subtypes, heralding a new era of "enhanced" precision oncology.
Insights
Protein kinases are key cancer drivers, but fully exploiting them for targeted therapies remains challenging. Advances in proteomics and multi-omic data are unlocking new precision oncology strategies by revealing complex kinase signaling networks.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Protein kinases are validated oncogenic drivers and targets for cancer therapy.
- The full potential of the human kinome for precision oncology is not yet realized due to challenges in detecting kinase dysregulation and characterizing the kinome.
- Targeting specific kinases requires comprehensive mapping of kinome-wide drug effects.
Purpose of the Study:
- To explore the potential of the human kinome as a source of actionable cancer targets.
- To address limitations in current precision oncology approaches for kinase-targeted therapies.
- To leverage advancements in proteomics and multi-omic data for enhanced cancer therapy.
Main Methods:
- Utilizing mass spectrometry-based phosphoproteomics and kinomics to analyze protein kinase activity.
- Integrating multi-omic data, including genomic, transcriptomic, and (phospho)proteomic data from initiatives like the Clinical Proteomic Tumour Analysis Consortium.
- Mapping the total kinome space affected by small molecule drugs.
Main Results:
- Recent proteomics developments provide tools to overcome impediments in kinome analysis.
- Multi-omic data integration offers unprecedented insights into oncogenic kinases and cancer cell signaling.
- Novel therapeutic targets and drug repurposing opportunities are being identified.
Conclusions:
- Advancements in proteomics and multi-omic data analysis are crucial for enhanced precision oncology.
- These approaches are identifying new therapeutic targets and optimizing treatment strategies for specific cancer subtypes.
- A new era of precision oncology, driven by a deeper understanding of kinase signaling, is emerging.
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